1. Endoplasmic reticulum stress contributed to β1-adrenoceptor autoantibody-induced reduction of autophagy in cardiomyocytes.
- Author
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Wang L, Ning N, Wang C, Hou X, Yuan Y, Ren Y, Sun C, Yan Z, Wang X, and Liu H
- Subjects
- Animals, Apoptosis, Cell Line, Cells, Cultured, Male, Myocytes, Cardiac immunology, Rats, Sprague-Dawley, Autoantibodies immunology, Autophagy, Endoplasmic Reticulum Stress, Myocytes, Cardiac cytology, Receptors, Adrenergic, beta-1 immunology
- Abstract
Autophagy reduction has been confirmed as an important mechanism in apoptosis induction. Our previous study showed that decreased autophagy induced by β1-adrenoceptor autoantibodies (β1-AAs) enhanced cardiomyocyte apoptosis and contributed to heart failure progression. Endoplasmic reticulum stress (ERS) is known to be an important mechanism in intracellular homeostasis and is closely related to autophagy. However, ERS in β1-AA-induced autophagy dysfunction of cardiomyocytes remains unclear. In this study, we used an active immunization rat model and H9c2 cardiomyocytes to study the role of ERS in β1-AA-induced autophagy. Results showed that prolonged action of β1-AAs significantly reduced the autophagy of myocardial tissues and H9c2 cardiomyocytes, and ERS and its related apoptotic pathways were significantly activated. Moreover, mRFP-GFP-LC3 double-labeled adenoviruses were used to detect cardiomyocyte autophagic flux to confirm that β1-AAs caused a significant decrease in autophagic flux in H9c2 cardiomyocytes. The ERS inhibitor, 4-phenylbutyrate (4-PBA), partially attenuated the β1-AA-induced reduction of cardiomyocyte autophagy, consistent with the effect of the mammalian target of rapamycin inhibitor rapamycin (Rapa). Compared to the pretreatment with 4-PBA or Rapa alone, pretreatment with the combination of 4-PBA and Rapa had a greater effect on attenuating the β1-AA-induced decrease in autophagy and β1-AA-induced apoptosis in cardiomyocytes. This study provides an experimental basis for the role of β1-AAs in the homeostatic maintenance of cardiomyocytes in patients with heart failure with respect to autophagy and ERS., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2019
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